We have recently shown that the synthesis of the enzyme ribonucleotide reductase, the first enzyme unique to the pathway leading to DNA synthesis, is controlled in the same way as initiation of DNA replication in Escherichia coli. The enzyme is synthesized once per generation at the time of DNA initiation. We plan to study the regulation of the synthesis of this enzyme in yeast by using the numerous cell cycle mutants available as well as alpha-factor which can be used to synchronize yeast cells. We plan to continue studying the synthesis of the m-RNA for this enzyme by using DNA-RNA hybridization. Another area that we plan to investigate is the enzyme system that couples NADPH oxidation to reduction of ribonucleotides by using genetic as well as biochemical techniques. We will exploid a mutant defective in thymidine monophosphate kinase that we have isolated to better our understanding of control of deoxyribonucleotide metabolism.